Integrative landscape of dysregulated signaling pathways of clinically distinct pancreatic cancer subtypes

Oncotarget
Musalula SinkalaDarren Patrick Martin

Abstract

Despite modern therapeutic advances, the survival prospects of pancreatic cancer patients have remained poor. Besides being highly metastatic, pancreatic cancer is challenging to treat because it is caused by a heterogeneous array of somatic mutations that impact a variety of signaling pathways and cellular regulatory systems. Here we use publicly available transcriptomic, copy number alteration and mutation profiling datasets from pancreatic cancer patients together with data on disease outcomes to show that the three major pancreatic cancer subtypes each display distinctive aberrations in cell signaling and metabolic pathways. Importantly, patients afflicted with these different pancreatic cancer subtypes also exhibit distinctive survival profiles. Within these patients, we find that dysregulation of the phosphoinositide 3-kinase and mitogen-activated protein kinase pathways, and p53 mediated disruptions of cell cycle processes are apparently drivers of disease. Further, we identify for the first time the molecular perturbations of signalling networks that are likely the primary causes of oncogenesis in each of the three pancreatic cancer subtypes.

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Citations

Nov 23, 2019·Communications Biology·Musalula SinkalaDarren Patrick Martin
Mar 3, 2020·Mutation Research·M IidaM Toulany
Jan 12, 2020·Communications Biology·Musalula SinkalaDarren Patrick Martin
Sep 11, 2021·PloS One·Doris KafitaMusalula Sinkala

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Methods Mentioned

BETA
protein array
integrative profiling
RNAseq
RNA-seq
Immunoprecipitation

Software Mentioned

Enrichr
BioGrid
MutSigCV
GSEA
Reactome
Enrichment Map
Kinase Enrichment Analysis ( KEA
MATLAB
TieDIE
Expression2Kinases

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